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Impairment of Body Growth in Mucopolysaccharidoses

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Handbook of Growth and Growth Monitoring in Health and Disease

Abstract

Children with mucopolysaccharidoses (MPS) grow poorly and become physically handicapped because of systemic bone disease. For children with skeletal dysplasias, such as MPS, it is important to know the natural history of growth. Understanding of the growth pattern provides assessment of current growth and data on efficacy of individualized medicine in growth-promoting treatments. The purpose of this chapter is to review natural history of growth patterns for MPS II, IVA, and VI patients. The cross-sectional and/or longitudinal data were collected to develop growth curves for the following types of MPS. Interestingly, accelerated growth has been observed in the first years of life in any type of MPS reviewed here, followed by slowing growth rate and growth failure. (1) MPS II: We obtained height and weight measurements from 46 Japanese male patients with MPS II. Mean birth length of boys was 50.9 ± 2.1 cm. The mean height for MPS II at 18 years of age or older was 127.2 ± 8.5 cm. These values corresponded to 0.9 SD and −7.5 SD of the height for normal Japanese males. The mean height was kept higher until 5 years and the mean weight was heavier until 8 years of age. After 7 years of age, short stature was commonly observed in spite of clinical severity by CNS involvement. (2) MPS IVA: Height and weight measurements from 193 girls and 195 boys with MPS IVA were collected. Mean birth lengths of boys and girls were 52.4 ± 3.9 and 52.1 ± 2.9 cm, respectively. Mean heights for males and females at 18 years of age were 119.3 ± 22.6 and 113.5 ± 23.1 cm, respectively. These values correspond to −8.0 SD and −7.7 SD of the mean height for normal males and females. Mean birth weights for boys and girls were 3.56 ± 0.5 and 3.5 ± 0.7 kg, respectively. (3) MPS VI: Growth is severely impacted on this type of MPS. In an observational study in 121 untreated MPS VI patients, a mean height was 115.2 cm ± 26.1 cm and median height was 103.7 cm with a range of 80–169 cm. An inverted correlation of height with the excretion of urinary GAGs and an influence of the genotype on the pattern of this excretion were also demonstrated. Thus, the growth pattern in MPS II patients was characterized by impaired growth velocity after 4 years of age, while the growth patterns in MPS IVA and VI patients were characterized by impaired growth velocity after 1 and 2 years of age.

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Abbreviations

BMI:

Body mass index

CDC:

Centers for Disease Control and Prevention

CS:

Chondroitin sulfate

DS:

Dermatan sulfate

ERT:

Enzyme replacement therapy

GAGs:

Glycosaminoglycans

GALNS:

N-Acetylgalactosamine-6-sulfate sulfatase

GH:

Growth hormone

HCT:

Hematopoietic cell transplantation

HS:

Heparan sulfate

IGF-1:

Insulin-like growth factor-1

IV:

Intravenous

KS:

Keratan sulfate

MPS:

Mucopolysaccharidoses

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Acknowledgments

This study was supported by grants from Ariana’s Cure Fund for Morquio, the Austrian Research Society for Mucopolysaccharidoses and Related Diseases, Bennett Foundation, Care for Carly Foundation, Care for Sota Morquio Foundation, German MPS Society, International Morquio Organization (Carol Ann Foundation), Italian MPS Society, Jacob Randall Foundation, Miracle for Eddie Foundation, National MPS Society, Muconetwork, and Spanish MPS Society. The MPS VI clinical trials were sponsored by BioMarin Pharmaceutical Inc., and supported, in part, with funds provided by the National Center for Research Resources, 5 M01 RR-01271 (Dr. Harmatz). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Conflict of Interest: Dr. Harmatz, has provided consulting support to Shire HGT and BioMarin Pharmaceutical Inc. Dr. Harmatz also report receiving a speaker’s honorarium and travel support from BioMarin, Shire and Genzyme.

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Authors and Affiliations

  1. Department of Pediatrics, Saint Louis University, St. Louis, MO, 63104, USA

    Shunji Tomatsu, Adriana M. Montaño & Hirotaka Oikawa

  2. Medical Genetics Service/HCPA, Rua Ramiro Barcelos 2350, Porto Alegre, RS, 90630-080, Brazil

    Roberto Giugliani

  3. Children’s Hospital & Research Center Oakland, Oakland, CA, 94609, USA

    Paul Harmatz

  4. International Morquio Organization, Phoenix, AZ, USA

    Mary Smith

  5. Department of Pediatrics, Gifu University School of Medicine, Gifu, 501 1194, Japan

    Yasuyuki Suzuki & Tadao Orii

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  1. Shunji Tomatsu
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Correspondence to Shunji Tomatsu .

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  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

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Tomatsu, S. et al. (2012). Impairment of Body Growth in Mucopolysaccharidoses. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_126

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